How similar are the treatment responses to biosimilars in patients with psoriasis? A systematic review of statistical margins in comparative clinical trials.
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ABSTRACT:
SUBMITTER: Wan MT
PROVIDER: S-EPMC5605927 | biostudies-literature | 2017 Sep
REPOSITORIES: biostudies-literature
Publications
How similar are the treatment responses to biosimilars in patients with psoriasis? A systematic review of statistical margins in comparative clinical trials.
Wan Marilyn T MT Strober Bruce E BE Wu Jashin J JJ Shin Daniel B DB Gelfand Joel M JM
Journal of the American Academy of Dermatology 20170901 3
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Project description:ImportanceBiologics account for almost half of US drug spending but may be subject to competitive pricing pressures by US Food and Drug Administration-approved biosimilars. The extent of the preapproval clinical testing that is needed and how these biosimilars compare with the originator biologic products remain critical issues in establishing a vibrant biosimilar market.ObjectivesTo analyze the design of cancer biosimilar efficacy studies compared with the reference drug pivotal trials and provide summary risk ratio estimates for each cancer type drug subgroup.Data sourcesA systematic search was performed of articles and abstracts published using Embase, PubMed/MEDLINE, and ClinicalTrials.gov, last updated April 18, 2021.Study selectionAll studies or abstracts in English comparing a disease-modifying cancer biologic and its biosimilar and reporting efficacy or surrogate efficacy results were included.Data extraction and synthesisOutcome estimates and study characteristics were extracted from each study. Among biosimilar efficacy studies, random-effects meta-analyses were performed for each cancer type molecule outcome subgroup, calculating pooled relative estimates and 95% CIs.Main outcomes and measuresStudy characteristics, such as population size, blinding, and randomization, were compared between biosimilar trials and those of reference drugs. Risk ratio estimates for relative change to surrogate measures (eg, progression-free survival) were collected for biosimilars and their reference products.ResultsA total of 31 cancer biosimilar studies of 3 reference products involving 12 310 patients were included. In all 7 subgroups, the biosimilars analyzed were indistinguishable from their reference drug on surrogate efficacy. Six reference drug trials were included, involving 1811 patients. On average, biosimilar studies involved more patients than reference drug trials (mean number of patients, 397 vs 302), were more likely to be randomized clinical trials rather than single-group or observational studies (100% [31 of 31] vs 50% [3 of 6]), and were more likely to be double blind rather than open label (84% [26 of 31] vs 17% [1 of 6]).Conclusions and relevanceThis systematic review and meta-analysis found that the biosimilars for the cancer drugs in this sample were subjected to rigorous clinical evaluations, and the results were statistically indistinguishable from those of original products across drugs, cancer types, and outcome measures.
| S-EPMC8814981 | biostudies-literature
Project description:AimIn 2006, Omnitrope (by Sandoz) was the first approved biosimilar in Europe. To date, 21 biosimilars for seven different biologics are on the market. The present study compared the clinical trials undertaken to obtain market authorization.MethodsWe summarized the findings of a comprehensive review of all clinical trials up to market authorization of approved biosimilars, using the European public assessment reports (EPARs) published by the European Medicines Agency (EMA). The features compared were, among others, the number of patients enrolled, the number of trials, the types of trial design, choice of endpoints and equivalence margins for pharmacokinetic (PK)/pharmacodynamic (PD) and phase III trials.ResultsThe variability between the clinical development strategies is high. Some differences are explainable by the characteristics of the product; if, for example, the PD marker can be assumed to predict the clinical outcome, no efficacy trials might be necessary. However, even for products with the same reference product, the sample size, endpoints and statistical models are not always the same.ConclusionsThere seems to be flexibility for sponsors regarding the decision as to how best to prove biosimilarity.
| S-EPMC5099555 | biostudies-literature
Project description:Translational oncology research strives to explore a new aspect: identifying subgroups that exhibit treatment response even during pre-clinical phases. In this study, we focus on PDX models and their implementation in mouse clinical trials (MCT). Our primary objective was to identify subgroups with different treatment responses using Latent Class Mixed Model (LCMM).We used a public dataset and focused on one treatment, encorafenib, and two indications, melanoma and colorectal cancer, for which efficacy depends on a specific mutation BRAF V600E. One LCMM per indication was implemented to classify treatment responses at the PDX level, analyzing the growth kinetics of treated tumors and matched controls within the PDX models. A simulation study was carried out to explore the performance of LCMM in this context. For both applications, LCMM identified classes for which the higher the proportion of mutated BRAF V600E PDX models the greater the treatment effect, which is aligned with encorafenib use recommendations. The simulation study showed that LCMM could identify classes with large differences in treatment effects. LCMM is a suitable tool for MCT to explore treatment response subgroups of PDX. Once these subgroups are defined, characterization of their phenotypes/genotypes could be performed to explore treatment response predictors.
| S-EPMC10776864 | biostudies-literature
Project description:The goal of this narrative review was to summarize immunogenicity data of biosimilars or biosimilar candidates for rheumatic diseases, plaque psoriasis, or inflammatory bowel disease (IBD), available in peer-reviewed publications or regulatory documents. PubMed records and regulatory documents were searched for immunogenicity data of TNFα or CD20 inhibitor biosimilars or biosimilar candidates. Data collected included the proportion of patients positive for anti-drug antibodies (ADAbs), proportion with neutralizing antibodies (nAbs) among ADAb-positive patients, ADAb/nAb assay characteristics, cross-reactivity, and the effects of ADAbs on pharmacokinetics, pharmacodynamics, efficacy, and safety. We identified eight biosimilars or biosimilar candidates for adalimumab (BI 695501, SB5, ABP 501, GP2017, PF-06410293, MSB-11022, FKB-327, ZRC-3197) four for etanercept (SB4, GP2015, CHS-0214, LBEC0101), and three each for infliximab (SB2, CT-P13, GP1111) and rituximab (CT-P10, GP2013, PF-05280586) with immunogenicity data. Randomized, head-to-head trials with reference products varied in design and methodology of ADAb/nAb detection. The lowest proportions of ADAb-positive (0-13%) and nAb-positive patients (0-3%) were observed in the trials of etanercept and its biosimilars, and the highest with adalimumab, infliximab, and their biosimilars (ADAbs: ≤ 64%; nAbs: ≤ 100%). The most common method of ADAb detection was electrochemiluminescence, and ADAb positivity was associated with nominally inferior efficacy and safety. Overall, there were no significant immunogenicity differences between biosimilars and reference products. However, there are many discrepancies in assessing and reporting clinical immunogenicity. In conclusion, immunogenicity data of biosimilars or biosimilar candidates for TNFα or CD20 inhibitors were collected in trials that varied in design and procedures for ADAb/nAb detection. In general, immunogenicity parameters of biosimilars are similar to those of their reference products.
| S-EPMC7042210 | biostudies-literature
Project description:IntroductionPsoriasis is a chronic inflammatory skin disease. Adalimumab is an effective but previously expensive biological treatment for psoriasis. The introduction of biosimilars following the patent expiry of the originator adalimumab Humira has reduced the unit cost of treatment. However, the long-term effectiveness and safety of adalimumab biosimilars for treating psoriasis in real-world settings are uncertain and may be a barrier to widespread usage.Methods and analysisThis study aims to compare the drug survival and safety of adalimumab biosimilars to adalimumab originator for the treatment of psoriasis. We will use both routinely collected healthcare databases and dedicated pharmacovigilance registries from the PsoNet initiative, including data from the UK, France and Spain. We will conduct a cohort study using a prevalent new user design. We will match patients on previous adalimumab exposure time to create two equal-sized cohorts of biosimilar and originator users. The coprimary outcomes are drug survival, defined by the time from cohort entry to discontinuation of the drug of interest; and risk of serious adverse events, defined by adverse events leading to hospitalisation or death. Cox proportional hazards models will be fitted to calculate HRs as the effect estimate for the outcomes.Ethics and disseminationThe participating registries agree with the Declaration of Helsinki and received approval from local ethics committees. The results of the study will be published in scientific journals and presented at international dermatology conferences by the end of 2023.
| S-EPMC10351260 | biostudies-literature
Project description:Tyrosine kinase 2 (TYK2), a key part of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, plays an integral role in the differentiation and immune responses of intrinsic immune cells and regulates the mediation of cytokines. TYK2 leads to inflammatory cascade responses in the pathogenesis of immune-mediated inflammatory diseases (IMIDs), especially psoriasis. Small-molecule TYK2 inhibitors are considered to be an effective strategy for modulating psoriasis. Here, we attempt to review the pro-inflammatory mechanisms of the JAK-STAT signaling pathway, the regulatory roles of TYK2 in the pathogenesis of psoriasis, and provide updates on ongoing and recently completed trials of TYK2 inhibitors.
| S-EPMC9488612 | biostudies-literature
Project description:BackgroundBiologic treatments for cancer continue to place a significant economic burden on healthcare stakeholders. Biosimilar therapies may help reduce this burden through cost savings, thereby increasing patient access.ObjectivesThe purpose of this study was to collate all published data to assess the weight of available evidence (quantity and quality) for proposed monoclonal antibody biosimilars and intended copies, for the treatment of cancer.MethodsMEDLINE®, Embase®, and ISI Web of Science® databases were searched to September 2015. Conference proceedings (17) were searched (2012 to July 2015). Searches of the United States National Library of Medicine ClinicalTrials.gov registry were also conducted. Risk of bias assessments were undertaken to assess data strength and validity.ResultsProposed biosimilars were identified in 23 studies (36 publications) in oncology and ten studies in 14 publications in oncology and chronic inflammatory diseases for bevacizumab, rituximab, and trastuzumab originators. Based on our review of the included published studies, and as inferred from the conclusions of study authors, the identified proposed biosimilars exhibit close similarity to their originators. Published data were also retrieved on intended copies of rituximab. It remains unclear what role these agents may have, as publications on rigorous clinical studies are lacking for these molecules.ConclusionWhile biosimilar products have the potential to improve patient access to important biologic therapies, robust evidence of outcomes for monoclonal antibody biosimilars in treating cancer patients, including data from comparative efficacy and safety trials, is not yet available in the published literature. Significant data gaps exist, particularly for intended copies, which reinforces the need to maintain a clear differentiation between these molecules and true biosimilars. As more biosimilars become available for use, it will be important for stakeholders to understand fully the robustness of overall evidence used to demonstrate biosimilarity and gain regulatory approval.
| S-EPMC5258783 | biostudies-literature
Project description:IntroductionThe real-life effectiveness of adalimumab biosimilars in patients with psoriasis has rarely been investigated.ObjectiveTo investigate drug survival of adalimumab biosimilars in patients with chronic plaque psoriasis and factors associated with its discontinuation.MethodsWe carried out a retrospective observational study including all consecutive patients with chronic plaque psoriasis who initiated adalimumab biosimilar MSB11022 (Idacio), ABP501 (Amgevita), or SB5 (Imraldi) between 1 January 2018 and 1 January 2021. The 1-year drug survival of adalimumab biosimilar and independent factors associated with its discontinuation were investigated. Cox regression models were fit to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for the risk of adalimumab discontinuation. A propensity score matching (PSM) model was adopted as sensitivity analysis.ResultsThe study involved a total of 410 patients with follow-up of 549.84 person-years, 271 (66.1%) men, a mean (SD) age of 51.8 (14.5) years, and a baseline PASI of 14.54 (5.02). Among adalimumab biosimilars, 250 (61%) patients received MSB11022, 98 (24%) received ABP501, and 62 (15%) received SB5. Drug survival of adalimumab biosimilars at 1 year was 81.5% in the overall study population. Obesity was associated with increased risk of adalimumab discontinuation (HR = 2.01; 95% CI 1.33-3.03), whereas psoriatic arthritis (aHR = 0.32; 95% CI 0.16-0.64) and receiving adalimumab as first systemic treatment (aHR = 0.44; 95% CI 0.27-0.70) were associated with lower risk.ConclusionThe real-life effectiveness of adalimumab biosimilars in patients with psoriasis is consistent with that previously reported for the originator.
| S-EPMC9209594 | biostudies-literature
Project description:BackgroundPrevious observational studies have shown comorbidity between psoriasis and psychological disorders. However, the evidence of the efficacy of psychological interventions, including cognitive behavioral therapy (CBT) and other treatments, on psoriasis is still debated.ObjectivesThe aim of this study was to systematically review the psychological interventions used in the treatment of psoriasis and to meta-analyze the efficacy of psychological interventions on psoriasis with respect to area and severity reduction.Materials and methodsA systematic review and meta-analysis were conducted. PubMed, Web of Science, EMbase, and major Chinese academic journal databases were searched for articles published before January 2018. Studies of randomized controlled trials (RCTs) that applied psychological interventions in the treatment of psoriasis and used area and severity as the outcome measures were meta-analyzed. The pooled mean difference between groups was estimated using either fixed-effects models or random-effects models in the presence of heterogeneity. Subgroup analysis was performed by method of intervention and severity of psoriasis.ResultsOut of the 4,152 potentially relevant studies, 8 RCTs were included. The pooled mean difference was -1.36 (95% CI: -2.52 to -0.19; P=0.02). The pooled estimate was -1.80 (95% CI: -2.57 to -1.03; P<0.001) for CBT intervention and was -0.70 (95% CI: -2.39 to 0.99; P=0.42) for non-CBT intervention. The pooled estimates for mild and moderate-to-severe psoriasis were -1.95 (95% CI: -3.91 to 0.00; P=0.05) and -0.61 (95% CI: -1.61 to 0.38; P=0.23), respectively.ConclusionCBT is effective in the treatment of psoriasis in terms of area and severity reduction. Systemic treatment does not further enhance the efficacy of CBT. The effect of the psychological intervention is stronger in patients with moderate-to-severe psoriasis.
| S-EPMC6369842 | biostudies-literature
Project description:BackgroundThe reporting of randomised controlled non-inferiority (NI) drug trials is poor with less than 50% of published trials reporting a justification of the NI margin. This is despite the introduction of the Consolidated Standards of Reporting Trials (CONSORT) extension on reporting of NI and equivalence in randomised trials. It is critical to set the appropriate NI margin as this choice dictates the conclusions of the trial. Methods to estimate the margin are heterogeneous but generally based on clinical judgement and statistical reasoning, and hence tailored to each clinical situation. Yet an appraisal of NI in clinical trials has not been undertaken. Therefore the aim of this systematic review is to assess the reporting and methodological quality of defining the NI margin. Surgical NI trials have been chosen as our prototype to assess this.MethodsWe will conduct a systematic review of published randomised controlled trials in abdominal surgery that use an NI design. Key eligibility criteria will be: surgical intervention in at least one trial arm; adult patients and a sample size of 100 or more. Ovid MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials will be searched from inception until the date of the search. Identified studies will be assessed for reporting according to the CONSORT recommendations. The outcomes are the description of the methods for defining the NI margin, and the robustness of the NI margin estimation. The latter will be based on simulations using alternative assumptions for model parameters. The results of the simulation will be compared with the trial authors' conclusions.Anticipated resultsThe review will describe and appraise the design and reporting of surgical NI trials including shortcomings thereof and allow a comparison with pharmaceutical trials. These findings will inform researchers on the appropriate design and pitfalls when conducting surgical randomised controlled trials with an NI design and promote thorough and standardised reporting of study findings.Ethics and disseminationEthical approval is not required and any changes to the protocol will be communicated via the registration platform. The final manuscript will be submitted to a journal for publication and the findings will be disseminated through conference presentations to inform researchers and the public.
| S-EPMC11344494 | biostudies-literature